POS0572 IMMUNOGENICITY AND SAFETY OF ADJUVANTED RECOMBINANT ZOSTER VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS
Authors: S. Kojima, T. Iwamoto, Y. Kobayashi, M. Kato, F. Takizawa, T. Ida, Y. Toda, K. Miyachi, J. Suzuki, A. Iwata, S. Furuta, K. Ikeda, K. Suzuki, H. Nakajima
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) due to a decline in VZV-specific cell-mediated immunity (CMI) with increasing age and immunocompromised conditions [1]. Patients with rheumatoid arthritis (RA) treated with disease-modifying anti-rheumatic drugs (DMARDs) are at a high risk of developing HZ [2, 3]. An adjuvanted recombinant VZV glycoprotein E (gE) subunit vaccine (RZV) has been shown to be effective in preventing HZ in immunocompetent elderly populations. However, its efficacy and safety profile remain largely unknown in RA patients. <h3>Objectives</h3> This study aimed to determine the immunogenicity and safety of RZV in patients with RA treated with DMARDs. <h3>Methods</h3> This longitudinal prospective study enrolled 53 RA patients treated with DMARDs (csDMARDs, n=20; bDMARDs, n=23; and tsDMARDs, n=10) and 10 individuals with no history of immunosuppressive treatment as controls. All the participants were aged ≥50 years. The participants received two intramuscular RZV injections 2 months apart. VZV-specific CMI and humoral immunity (HI) were assessed at 0 and 3 months after the first vaccination using flow cytometry and enzyme immunoassay. To assess CMI, the frequencies of VZV gE-specific CD4<sup>+</sup> CD40L<sup>+</sup> T cells expressing at least one activation cytokine (CD4[2+] T cells): IFN-γ, IL-2, and TNF-α were examined by flow cytometry. CMI responders were defined as a CD4[2+] T cell frequency ≥320 per 10<sup>6</sup> CD4<sup>+</sup> T cells counted (for participants with pre-vaccination frequencies below 320 per 10<sup>6</sup> CD4<sup>+</sup> T cells counted) or a ≥2-fold increase in CD4[2+] T cells (for those CD4[2+] T cells were already ≥320 per 10<sup>6</sup> CD4<sup>+</sup> T cells counted at the time of pre-vaccination). CMI and HI response rates were compared between all patients with RA (n=53) and controls (n=10). The participants were followed up for 6 months after the first RZV administration for HZ onset. Baseline characteristics and information regarding adverse events were collected. <h3>Results</h3> Patients' age and disease duration were 70 years old and 11 years, respectively. DAS28-CRP and CDAI scores at enrollment were 1.4 and 2.1, respectively. Thirty-six percent of RA patients had a history of HZ before the administration of RZV. VZV-specific CMI (controls: p=0.002, csDMARDs: p=0.012, bDMARDs: p=0.001, and tsDMARDs: p=0.002) (Figure 1A) and HI (controls: p=0.002, csDMARDs: p&lt;0.001, bDMARDs: p&lt;0.001, tsDMARDs: p=0.002) were significantly increased in DMARDs-treated RA patients after RZV administration, and the magnitudes of those responses were not significantly different between DMARDs-treated RA patients and controls. However, the vaccine response rate of CMI of DMARDs-treated RA patients was significantly lower than that of the controls (51% vs. 90%, p=0.034) (Figure 1B), whereas the response rate of HI was not (66% vs. 70%, p&gt;0.999). In addition, no significant baseline factors affecting CMI responses, including DMARDs use, were identified between RA patients with and without CMI responses. RZV-related adverse events were generally mild, and all participants received two doses of RZV. RZV-induced RA flares occurred in two patients (3.8%) but were also mild and controllable. <h3>Conclusion</h3> RZV is robustly immunogenic and has a clinically acceptable safety profile in elderly RA patients receiving DMARDs. <h3>References</h3> [1]Cohen JI. N Engl J Med. 369, 255-263 (2013) [2]Veetil BM, et al. Arthritis Care Res (Hoboken). 65, 854-861 (2013) [3]Redeker I, et al. Ann Rheum Dis. 81, 41-47 (2022) [4]Strezova A, et al. Open Forum Infect Dis. 23, ofac485 (2022) <h3>Acknowledgements</h3> This work was supported in part by grants from Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response (SCARDA), Japan Agency for Medical Research and Development. <h3>Disclosure of Interests</h3> Shotaro Kojima: None declared, Taro Iwamoto: None declared, Yoshihisa Kobayashi: None declared, Manami Kato: None declared, Fumiyoshi Takizawa: None declared, Tomoaki Ida: None declared, Yosuke Toda: None declared, Kazusa Miyachi: None declared, Junya Suzuki: None declared, Arifumi Iwata: None declared, Shunsuke Furuta: None declared, Kei Ikeda Speakers bureau: KI has received research grants from Mitsubishi-Tanabe Pharma, all unrelated to the current manuscript., Grant/research support from: KI has received honoraria for lectures from Abbvie, Mitsubishi-Tanabe Pharma, Eli Lilly Japan, Novartis, Pfizer Japan, Janssen Pharmaceutical, Eisai, Gilead Sciences and Bristol Myers Squibb, all unrelated to the current manuscript., Kotaro Suzuki: None declared, Hiroshi Nakajima Speakers bureau: HN has received honoraria for lectures from Chugai Pharmaceutical, Abbvie, Takeda Pharmaceutical, Astellas Pharma, Eli Lilly Japan, Asahikasei Pharma, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Eisai, Bristol Myers Squibb and Nippon Kayaku, all unrelated to the current manuscript., Grant/research support from: HN has received research grants from Chugai Pharmaceutical, Abbvie, Takeda Pharmaceutical, Astellas Pharma, Eli Lilly Japan, Asahikasei Pharma, Pfizer Japan, UCB Japan, Eizai, Mitsubishi Tanabe Pharma and Bristol Myers Squibb, all unrelated to the current manuscript.